Phosphorus oxychloride → 2-Chloro-6-(4-methylphenyl)-5-phenylnicotinonitrile

HRID 2105513Notes

Reaction equation

HRID 2105513 reaction equation
[CH3:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[NH:13][C:12](=O)[C:11]([C:15]#[N:16])=[CH:10][C:9]=2[C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)=[CH:4][CH:3]=1.O=P(Cl)(Cl)[Cl:25]>>[Cl:25][C:12]1[N:13]=[C:8]([C:5]2[CH:6]=[CH:7][C:2]([CH3:1])=[CH:3][CH:4]=2)[C:9]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)=[CH:10][C:11]=1[C:15]#[N:16]

Participants

3

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 211032106-(4-Methylphenyl)-2-oxo-5-phenyl-1,2-dihydropyridine-3-carbonitrile

Product 1

HCID 211031982-Chloro-6-(4-methylphenyl)-5-phenylnicotinonitrile

Procedure

The mixture of 6-(4-methylphenyl)-2-oxo-5-phenyl-1,2-dihydropyridine-3-carbonitrile (2-3; 1.5 g, 5.24 mmol) in POCl3 (15 mL) was heated to 100 C for 3 h and concentrated. The residue was basified with sodium carbonate aqueous solution and extracted with CH2Cl2 (3×30 mL). The combined organic layer was dried, filtered and concentrated. The residue was purified by silica gel chromatography (5-10% EtOAc in hexane) to give 2-chloro-6-(4-methylphenyl)-5-phenylnicotinonitrile (2-4). 1H-NMR (500 MHz, CDCl3) δ 7.95 (s, 1H), 7.33-7.35 (m, 3H), 7.28 (d, J=8.3, 2H), 7.16-7.18 (m, 2H), 7.06 (d, J=7.9, 2H), 2.32 (s, 3H). LRMS m/z (M+H) Calcd: 305.2, found: 305.1.

Workup

  1. temperaturewas heated to 100 C for 3 h
  2. concentrationconcentrated
  3. extractionextracted with CH2Cl2 (3×30 mL)
  4. customThe combined organic layer was dried
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified by silica gel chromatography (5-10% EtOAc in hexane)

Sources & evidence

ORD record
ord-318a8aafe7cb4dc98f0dcb97e70315a3
Source dataset
uspto-grants-2009_08
Patent number
US07579355B2

Reaction notes

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